Effects of pregnenolone, cyanoketone, and equilenin on the human malignant trophoblast in vitro

Summary

Cultures of human malignant trophoblast cells were studied to determine the basis of inhibition of human chorionic gonadotropin (HCG) secretion and depletion of glycogen following incubation of the cells in the presence of pregnenolone (3β-hydroxypregn-5-en-20-one). Incubation of the cells for as long as 3 days with 5 or 10 μg of pregnenolone per ml resulted in decreased protein content, inhibition of DNA synthesis, diminished glucose utilization, and marked accumulation of acellular debris in the medium. These changes became more pronounced with time of incubation and were related to the dose of pregnenolone employed. The effect of pregnenolone on all of the parameters measured was mimicked and potentiated by either equilenin (3-hydroxy-1,3,5(10),6,8-estrapentaen-17-one) or cyanoketone (androst-5-en-2α-cyano-17β-hydroxy-4,4,17α-trimethyl-3-one), inhibitors of pregnenolone conversion to progesterone. These results suggested that the glycogenolysis and inhibition of HCG secretion that occur when the trophblast cells are incubated in the presence of pregnenolone result from toxicity rather than from cellular differentiation, and that prior conversion of pregnenolone to progesterone is not necessary for the manifestation of the toxicity.